Masaka study: repeated community surveys with HIV tests

In 1989, researchers funded by government of the United Kingdom (UK; specifically, the Medical Research Council and Overseas Development Administration) and approved by the Ugandan Ministry of Health and National Council of Science and Technology, began a series of repeated annual surveys in 15 villages in Masaka District in southwest Uganda.[1] During each annual survey, researchers took blood from all willing residents (including children in at least some years) to test for HIV. The study team did not tell people the results of these tests. People had to visit a nearby clinic for an additional test to find out if they were infected. Few people went. Before 2004, “approximately 10% of the population knew their HIV status.”[quote from page 223 in reference 2]

Masaka study’s Natural History Cohort

Beginning in 1990, the Masaka study invited adults who tested HIV-positive during annual surveys, their HIV-negative spouses, and a similar number of HIV-negative adults into a Natural History Cohort, asking them to attend a study clinic every three months.[3] The Masaka study didn’t tell Cohort members their HIV status; since the Cohort included both HIV-positive and HIV-negative adults, being in the cohort said nothing about whether a member was or wasn’t infected.

Researchers used the Natural History Cohort to watch people get sick and die: “We studied survival times, disease progression, and AIDS defining disorders.”[page 245 in reference 4] Treatment was not a priority: “All clinic staff were unaware of the HIV-1 serostatus of the participants, which…allowed unbiased reporting of symptoms and signs by clinicians.”[page 246 in reference 4] Beginning in 1995, researchers’ tested blood samples from people in the Cohort to see whether and how much HIV infections had damaged their immune systems (measuring numbers of CD4 cells per unit of blood). Researchers withheld this information from clinic staff to reduce “[T]he bias of diagnosing HIV/AIDS related conditions because they knew the participant was HIV infected…”[page 195 in reference 5]

The clinic was not equipped to treat AIDS: Drugs to prevent opportunistic infections that come with AIDS and antiretroviral drugs to treat AIDS were not available until 2004.[2] Clinic staff diagnosed and treated Cohort members with “basic laboratory facilities and standard drugs from the WHO essential drug list, which should be available in any health post throughout Africa.”[page 602 in reference 6]

During 1990-2000, cohort members survived a median of 9.2 months with AIDS, “similar to the average of 10 months reported in industrialized countries early in the HIV epidemic. However, the course of AIDS in developed countries has changed . . . through the use of prophylaxis and antiretroviral drugs. Survival after an AIDS diagnosis in the United Kingdom increased . . . to over 19 months in 1991.”[page 602 in reference 6] After years of holding back, the study belatedly provided AIDS-related treatments to members of the Natural History Cohort. According to a 2007 report: “Treatment for opportunistic infections is available. Primary prophylactic regimens and antiretroviral therapy have been available since 2004.”[page 1057 in reference 7]

Masaka study repeats ethical lapses in the Tuskegee study

The Masaka study’s Natural History Cohort was similar in many respects to the widely criticized Tuskegee study of “untreated syphilis in the male Negro” during 1932-72 in the United States.[9] In the Tuskegee study, the United States’ Public Health Service pair for researchers to follow and study African-American men with syphilis without treating their infection. Medical journals periodically and openly reported findings from the study. After 20 years, researchers reported syphilis reduced life expectancy by 17%. After 30 years, researchers writing for a 1964 medical journal appreciated that “An untreated population such as this offered an unusual opportunity to follow and study the disease over a long period of time,” and reported “The syphilitic group continues to have higher mortality and morbidity than the uninfected controls, with the cardiovascular system most often involved”[pages 792 and 794 in reference 9] The US Public Health Service stopped the study in 1972, but not until newspapers brought it to the attention of the non-medical public.[10]

Was the Masaka study worse than the Tuskegee study?

In Tuskegee, doctors followed African-American men syphilis — without telling them they had syphilis and without treating it — to see how they got sick and died. In one important respect, the Masaka study compares unfavourably to what happened in Tuskegee: Men in Tuskegee had tertiary syphilis and so were not a threat to infect others. In Masaka, researchers studied not only sickness and death in HIV-positive adults, but also HIV transmission from people who did not know they were infected to unsuspecting spouses and children.

Spouses: The Masaka team invited uninfected spouses of HIV-positive members of its Natural History Cohort to join the Cohort; through December 2005, researchers recorded new HIV infections in 22 spouses.[7] Repeated community surveys similarly observed new infections in spouses of persons who had tested HIV-positive in a previous survey: during 1989-1997, surveys identified new infections in 22 women and 12 men with HIV-positive partners.[11] Most of the HIV-positive partners didn’t know they were infected, and most of the HIV-negative partners didn’t know they were at risk. As of 1999, the Masaka team reported: “…less than 10% of all adults make use of counselling [to learn their HIV status]… [W]e do not know whether individuals who come for counselling share their test results with their spouse… Although we had only limited data on condom use, it is noteworthy that none of the HIV-negative adults in discordant marriages reported using a condom.”[page 1088 in reference 11]

Children: During 1989–2000, the Masaka project’s annual surveys recorded 218 children born to HIV-positive mothers – most of whom did not know they were infected – and 62 deaths among children born to HIV-positive mothers.[12] Several annual surveys tested children for HIV. The 1999-2000 survey identified 6 HIV-positive babies whose mothers had tested HIV-positive in a previous survey.[2]